ACTIVITY OF ANGIOTENSIN-CONVERSING ENZYME-2 IN ACUTE PULMONARY INFLAMMATION

Relevance. Angiotensin converting enzyme-2 (ACE2), which is the gateway to coronavirus, is also an important component of the tissue renin-angiotensin system with a number of anti-inflammatory effects. It is known that ACE2 is expressed in the lungs of patients with coronavirus pneumonia, but it is not clear how this depends on the stages of development and the severity of inflammation. Objective: to establish the effect of acute inflammation on pulmonary expression of angiotensin-converting enzyme-2. Material and methods. In Wistar rats (n=20), in compliance with bioethical standards, a sterile nylon thread 2.5 cm long and 0.2 mm thick to a depth of 2.5 cm was introduced into the trachea. The animals were observed and removed from the experiment at 7, 14, 21 and 28 days, microscopic and immunohistochemical (monoclonal antibodies against ACE2; clone 4G5.1; EMD Millipore Corporation; Temecula, CA US) studies were performed. Results. The microscopic picture of the lungs indicated the development of acute bronchopulmonary inflammation during the first week, the formation of peribronchial and alveolar abscesses in the second week with the onset of resolution of bronchopneumonia with the organization of abscesses in the third week and the development of diffuse fibrosis of the parenchyma and vascular hyalinosis in the fourth week of observation. The exudative phase of acute inflammation was accompanied by inhibition of ACE2 activity in bronchial epithelial cells, type II alveolocytes and vascular endothelium. With the transition of inflammation to the stage of proliferation and fibrosis, ACE2 activity was restored. Conclusion. The detected phase change in ACE2 activity can cause a wavy recurrent course of coronavirus infection, since an increase in the amount of ACE2 protein during attenuation of acute inflammation contributes to an increase in target cell infection.

Influence of solution of lactoprotein with sorbitol on ultrastructural changes in lungs of rats in the condition of burn shock

This article gives a theoretical substantiation and a new experimental solution of a scientific problem aimed at increasing the effectiveness of pharmacotherapy on the morphofunctional state of the lungs of rats under conditions of burn shock by using a combined colloid-hyperosmolar infusion solution – lacto-protein with sorbitol. The administration of the test solution at a dose of 10 ml/kg for 7 days in rats with modelled burn shock reduced ultrastructural changes in the lungs triggered by burn shock. It has been proved that in the conditions of shock, colloid-hyperosmolar infusion lacto-protein with sorbitol solution facilitates the restoration of vascular endothelium and fluid retention in the microcirculatory channel and improves the morphofunctional state of the aerohematic barrier of the lungs, stimulates the activity of the alveolar macrophages and the secretory function of the type II alveolocytes producing surfactant. At day 7 of burn shock, when 0.9% of NaCl was injected, significant changes were observed in the respiratory unit: part of the alveoli had considerably enhanced clearance of blood capillaries, which had platelets, neutrophils and altered forms of erythrocytes. At day 7 of burn shock in the lungs of the rats given an infusion of colloid-hyperosmolar solution – lactoprotein with sorbitol, the ultrastructure of the components of the lung cells had improved in comparison with 3 days. Luminosity of the hemocapillary parts was moderate, mainly with erythrocytes. The walls of endothelial cells had elongated nuclei with invaginations of nuclear membranes and clear contours. Their cytoplasmic regions were not widespread, with moderate electron densities. In type II alveolocytes, during this experiment, a lower degree of damage to the nucleus and organelles in the cytoplasm was established, and there were signs of a renewal of the secretory function of these cells. In the cytoplasm, hypertrophied mitochondria with clear crystals, different sizes of secretory granules, which had a different density, indicating their formation, were observed. According to the magnitude of the cytoprotective effect on lung cells under conditions of burn shock, the lactoprotein with sorbitol solution was shown to be superior in comparison with the physical solution (0.9% NaCl). The study of functional, biochemical and molecular genetic parameters that characterize the state of the aerohematic barrier under the conditions of using lactoprotein with sorbitol solution in the case of burn injuries of the skin will allow researchers to comprehensively evaluate the mechanisms of the pulmonary protective effect of this preparation and to experimentally substantiate the expediency of its use in clinical practice for pharmaco-correction of burn shock.